There is evidence that secretion effects insulin release under certain in vitro and in vivo conditions. Whether this effect has physiologic significance for the maintenance of glucose homeostasis remains uncertain. Indirect methods of investigation have failed to solve this question and no suitable technique for the direct measurement of secretin has been available. We have recently developed a specific and reproducible radioimmunoassay for the direct determination of secretin in serum. The goal of this research is to use this new assay method to investigate the influences of endogenous secretin secretion on insulin and glucose regulation in man. Concerted effort will be directed toward the investigation of: 1) the influence of endogenous release of secretin on circulating levels of insulin and blood sugar in normal subjects; 2) the possibility that abnormalities in secretin secretion may be present in patients with diabetes mellitus or idiopathic hypoglycemia.